Studies in this laboratory are designed to elucidate the role of DNA repair processes in human diseases and in carcinogenesis, mutagenesis and aging. Most studies have been conducted with cells from patients with xeroderma pigmentosum (XP), all of whom have defective DNA repair plus the clinical abnormalities of multiple cutaneous malignancies and premature aging of sun-exposed skin. The DNA excision repair process is measured by assays of UV-induced unscheduled DNA synthesis. We assess the biological effectiveness of DNA repair by in vitro assays of post-irradiation colony-forming ability and trypan blue exclusion. We continue to classify XP cells into the appropriate genetic form of the disease by fusing fibroblasts to each other and measuring the UV-induced unscheduled DNA synthesis in the fused cells autoradiographically. We are extending our work to include cells from patients with other diseases in which DNA repair defects are claimed or suspected, such as Cockayne's syndrome, ataxia-telangiectasia, Fanconi's anemia, Werner's syndrome, Rothmund-Thompson syndrome, progeria, Bloom's syndrome and dyskeratosis congenita.